Patients with a Bicuspid Aortic Valve (BAV) Diagnosed with ECG-Gated Cardiac Multislice Computed Tomography-Analysis of the Reasons for Referral, Classification of Morphological Phenotypes, Co-Occurring Cardiovascular Abnormalities, and Coronary Artery Stenosis.

: The aim of this study was to analyze a group of patients with a bicuspid aortic valve (BAV) examined with ECG-gated cardiac CT (ECG-CT), focusing on the assessment of the clinical reasons for cardiac CT, cardiovascular abnormalities coexisting with their BAV, and coronary artery stenosis. : A detailed statistical analysis was conducted on 700 patients with a BAV from a group of 15,670 patients examined with ECG-CT. : The incidence of a BAV in ECG-CT was 4.

Seven-membered N-heterocycles as approved drugs and promising leads in medicinal chemistry as well as the metal-free domino access to their scaffolds.

Azepanes or azepines are structural motifs of many drugs, drug candidates and evaluated lead compounds. Even though compounds having N-heterocyclic 7-membered rings are often found in nature (e.g.

Cascade Transformation of the Ansamycin Benzoquinone Core into Benzoxazole Influencing Anticancer Activity and Selectivity.

The metal-free cascade transformation of geldanamycin benzoquinone core is proposed at relatively mild conditions. This approach yields new benzoxazole ansamycin antibiotics and enables their functionalization in an atom-economic manner, irrespective of the type of amine used. The analysis of the heterocyclization course reveals the dependence of its rate on the nature of the -substituent within the benzylamine moiety (EDG/EWG) and the strength of the base.

Modifications of geldanamycin via CuAAC altering affinity to chaperone protein Hsp90 and cytotoxicity.

Functionalization of alkyne (1) and azide (2) derivatives of geldanamycin (GDM) via dipolar cycloaddition CuAAC yielded 35 new congeners (3-37) with C(17)-triazole arms bearing caps of different nature (basic vs. acidic, hydrophilic vs. hydrophobic).

Outcomes of Open Repair Treatment for Acute Versus Chronic Achilles Tendon Ruptures: Long-Term Retrospective Follow-Up of a Minimum 10 Years-A Pilot Study.

The aim of the present study was to compare repaired Achilles tendon (AT) remodelling, whether its function was restored and what effects the surgery had on our patients' gait cycle in a long-term follow-up study. The study population comprised 30 human subjects treated acutely and chronically for AT ruptures, using the same surgical technique in all cases. The study group was divided into two subgroups regarding the age of their AT injury, i.

Cascade synthetic strategies opening access to medicinal-relevant aliphatic 3- and 4-membered N-heterocyclic scaffolds.

Cascade reactions are often 'employed' by nature to construct structurally diverse nitrogen-containing heterocycles in a highly stereoselective fashion, i.e., secondary metabolites important for pharmacy.

Factors Affecting Dental Caries Experience in 12-Year-Olds, Based on Data from Two Polish Provinces.

(1) Background: Dental caries is a chronic disease that affects a child’s dentition from the first stages of life. Several factors contribute to the development of the disease, including an improper diet. This cross-sectional study aimed to identify risk factors of dental caries in 12-year-old adolescents from Greater Poland and Lubusz Provinces (Poland).

Tandem construction of biological relevant aliphatic 5-membered N-heterocycles.

Nature often uses cascade reactions in a highly stereocontrolled manner for assembly structurally diverse nitrogen-containing heterocyclic scaffolds, i.e. secondary metabolites, important for medicinal chemistry and pharmacy.

Structural diversity and biological relevance of benzenoid and atypical ansamycins and their congeners.

Covering: 2011 to 2021The structural division of ansamycins, including those of atypical cores and different lengths of the ansa chains, is presented. Recently discovered benzenoid and atypical ansamycin scaffolds are presented in relation to their natural source and biosynthetic routes realized in bacteria as well as their muta and semisynthetic modifications influencing biological properties. To better understand the structure-activity relationships among benzenoid ansamycins structural aspects together with mechanisms of action regarding different targets in cells, are discussed.

Modifications, biological origin and antibacterial activity of naphthalenoid ansamycins.

Covering: 2011 to 2021Structural division of natural naphthalenoid ansamycins, regarding the type of the core and length of the ansa chain, and their biosynthetic pathways in microorganisms are discussed. The great biosynthetic plasticity of natural naphthalenoid ansamycins is reflected in their structural variety due to the alterations within ansa bridge or naphthalenoid core portions. A comparison between the biological potency of natural and semisynthetic naphthalenoid ansamycins was performed and discussed in relation to the molecular targets in cells.

Regioselective approach to colchiceine tropolone ring functionalization at C(9) and C(10) yielding new anticancer hybrid derivatives containing heterocyclic structural motifs.

The influence of base type, temperature, and solvent on regioselective C(9)/C(10) "" modifications within the tropolone ring of colchiceine () is investigated. New ether derivatives of , bearing alkyne, azide, vinyl, or halide aryl groups enable assembly of the alkaloid part with heterocycles or important biomolecules such as saccharides, geldanamycin or AZT into hybrid scaffolds by dipolar cycloaddition (CuAAC) or Heck reaction. Compared to colchicine () or colchiceine (), ether congeners, as e.

An Approach to Modify 14-Membered Lactone Macrolide Antibiotic Scaffolds.

A ketolide derivative with (12)-configuration was obtained via a novel ketene acetal in acidic conditions. The structure of this atypical β-keto ketene acetal intermediate within the macrocyclic system has been determined by NMR and X-ray methods. The use of basic conditions at an elevated temperature yielded new, doubly α,β-unsaturated ketone macrolide derivatives with (4)-configuration as two conformational isomers of folded-in or folded-out conformations.

Anticancer activity and toxicity of new quaternary ammonium geldanamycin derivative salts and their mixtures with potentiators.

Geldanamycin () has been modified by different type neutral/acidic/basic substituents (-) and by quinuclidine motif (), transformed into ammonium salts (-) at C(17). These compounds have been characterised by spectroscopic and x-ray methods. Derivative shows better potency than in MCF-7, MDA-MB-231, A549 and HeLa (ICs = 0.

Clinical Consequences of Dental Caries, Parents' Perception of Child's Oral Health and Attitudes towards Dental Visits in a Population of 7-Year-Old Children.

This cross-sectional study aimed to assess the occurrence of the consequences of dental caries and factors affecting dental service utilization in a population of 7-year-old children. The research included oral examination of 7-year-old schoolchildren and socio-medical study of their parents/legal caregivers. It was carried out in five primary schools of two provinces, i.

Synthesis, structure and anticancer activity of new geldanamycin amine analogs containing C(17)- or C(20)- flexible and rigid arms as well as closed or open ansa-bridges.

The nucleophilic attack of amines at C(17) or C(17)/C(20) positions of geldanamycin's (GDM) benzoquinone, via initial 1,4-Michael conjugate addition mechanism, yield new analogs with closed or open ansa-bridges (1-31), respectively. X-ray structures of analogs 22 and 24 reveals an unexpected arrangement of the ansa-bridge in solid (conformer B), that is located between those of conformers A, prevailing in solution (trans-lactam), and C, crucial at binding to Hsp90 (cis-lactam). The structure of a new-type conformer B allows to better understand the molecular recognition mechanism between the GDM analogs and the target Hsp90.

Synthesis and Antibacterial Activity of New N-Alkylammonium and Carbonate-Triazole Derivatives within Desosamine of 14- and 15-Membered Lactone Macrolides.

Desosamines of azithromycin (AZM) and clarithromycin (CLA) were modified by N-alkylation or nucleophilic substitution at the carbonyl/CuAAC sequence. Biological studies revealed a higher antibacterial potency of quaternary N-alkylammonium bromides of CLA as compared to AZM. SAR studies of CLA salts, including biological, conformation and molecular-docking analysis, enriched by physicochemical parameters, showed the importance of less bulky and unsaturated substituent for an efficient docking mode at the ribosomal tunnel and good antibacterial potency against clinical and standard Streptococcus pneumoniae and Streptococcus pyogenes strains (MICs 0.

Stress radiography in the diagnosis and assessment of the outcomes of surgical treatment of chronic anterolateral ankle instability.

Background: In about 20-40% of patients, damage to the soft tissues surrounding the ankle leads to recurrent and chronic pain with signs of instability of the talus in the tibiofibular fork.

Purpose: The aim of the study was to assess the usefulness of stress X-ray images in the diagnosis of long-term outcomes of conservative versus surgical treatment of anterolateral ankle instability.

Material And Methods: Thirty patients with chronic ankle instability (CAI) were recruited for the study.

14- and 15-membered lactone macrolides and their analogues and hybrids: structure, molecular mechanism of action and biological activity.

Classical macrolides containing 14- or 15-membered aglycone lactone rings are basic and widely used antibacterial agents in clinical therapy. Macrolides exert antibacterial effects by blocking the exit peptide tunnel during translation at bacterial ribosomes. However, one macrolide occasionally manifests different docking modes or binding sites at ribosomes, which presents difficulties in designing macrolide modifications.

Specific Interactions between Rifamycin Antibiotics and Water Influencing Ability To Overcome Natural Cell Barriers and the Range of Antibacterial Potency.

Rifamycins are a group of macrocyclic antibiotics mainly used for the treatment of various bacterial infections including tuberculosis. Spectroscopic studies of rifamycins evidence the formation of temperature- and solvent-dependent equilibria between A-, B-, and C-type conformers in solutions. The B- and C-type conformers of rifamycin antibiotics are exclusively formed in the presence of water molecules.

Antifungal, anticancer, and docking studies of colchiceine complexes with monovalent metal cation salts.

Complexes of colchiceine with monovalent cation perchlorates and iodides have been obtained and characterized by spectroscopic methods. DFT and spectroscopic studies reveal that the dihedral angle ω , crucial for colchicine biological mechanism of action, that is, binding to tubulins depends on the diameter of the complexed metal cation. Biological tests indicated no antifungal properties of colchicine (it was active only toward A.

Synthesis, docking and antibacterial studies of more potent amine and hydrazone rifamycin congeners than rifampicin.

New rifamycin congeners (1-33) with incorporated amine and hydrazone substituents leading to lipophilic and/or basic nature and altered rigidity of modified C(3) arm were synthesized and structurally characterized in detail. NMR spectroscopic studies at different temperatures indicate two types of structures of rifamycin congeners that are realized in solution: zwitterionic and non-ionic forms in dependence of the basicity of modified C(3) arm. The presence of rifamycin congeners in these two possible forms has a significant impact on the physico-chemical parameters such as lipophilicity (clogP) and water solubility and different binding mode of the C(3) arm of antibiotic at RNAP binding pocket (molecular target) leading to different antibacterial potency.

The mechanism of activation of amidobenzylidene ruthenium chelates - latent catalysts of olefin metathesis.

Amidobenzylidene ruthenium chelates - latent catalysts of olefin metathesis can be easily activated by the addition of Brønsted or Lewis acids. Their activation in the presence of hydrogen chloride involves the formation of catalytically active trans-dichloro carbamatobenzylidene ruthenium chelates.

Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.

Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency.

Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.

16-Membered Macrolide Lactone Derivatives Bearing a Triazole-Functionalized Arm at the Aglycone C13 Position as Antibacterial and Anticancer Agents.

A series of new C13-triazole-bridged and C13-ether leucomycin analogues with a reduced aldehyde group were synthesized. Derivatives with the highest antibacterial [MIC values (S. epidermidis, S.